Chapter 3ADME Pharmacogenetics and Its Impact on Drug–Drug Interactions

Abstract

3.1 Introduction

pharmacogenetics的关注重点已由最开始的药物代谢酶(M)，扩展到影响ADE的膜转运体

Genetic variants not only determine to which extent a drug is metabolized, taken up or excreted by ADME genes, but they also influence the various mechanisms of how two or more drugs interact with the resulting protein.

为了治疗comorbid symptoms，antipsychotics和antidepressants常需同时服用。Antidepressants，例如paroxetine和fluoxetine是CYP2D6的potent inhibiors，而2D6又负责许多antipsychotic medications的代谢，这些抗精神药物大多具有很窄的治疗窗。研究显示此种DDI会提高锥体束外综合征（extrapyramidal symptoms）的发生频率，或使其恶化; more likely to be seen in EMs.

it is worthwhile to note that enzyme activity also varies broadly among EMs.

许多药物涉及多个代谢途径和转运体，should be viewed and evaluated as an integrative system rather than single components.